Target cells or models Major effects Ref. Direct antitumor effects AML cells implanted in NOD/SCID/Il-2rγ −/− mice IL-27 suppressed human pediatric AML cell expansion, survival, and invasive properties [21 ] NSCLC cells in xenotransplant models IL-27 downregulated stemness and EMT genes in human NSCLC cells and activates intratumor myeloid cells to exert antitumor effects [22 ] PC3 or DU145 human prostate cancer cell injection in athymic nude mice IL-27 treatment reduced proliferation and vascularization in association with ischemic necrosis of tumors [23 ] Human multiple myeloma xenotransplant models IL-27 treatment suppressed angiogenesis, osteoclast differentiation, and bone erosive activity, while it supported osteoblast proliferation [24 ] Human ovarian cancer, neuroblastoma IL-27 induced HLA class-I antigen presentation machinery component expression and surface HLA class-I molecules and inhibited survival and migration of ovarian cancer cells [25 ] SKOV3 human ovarian cancer cell line The overexpression of IL-27 enhanced cell death and inhibited the proliferation of SKOV3 cells [26 ] Human NSCLC cells The combined use of the COX-2 inhibitor Apricoxib and IL-27 cooperatively inhibited EMT transition [27 ] Human NSCLC cells IL-27 suppressed epithelial-mesenchymal transition and expression of proangiogenic factors [28 ] Mouse melanoma B16F10 cell transfectants expressing wild-type WSX1 IL-27 showed antiproliferative activity on melanomas through WSX1/STAT1 signaling [29 ] Human melanoma in immunodeficient mice Combination of IL-27 with the TLR3 ligand poly (I:C) cooperatively suppressed melanoma growth [30 ] Indirect antitumor effects by targeting the tumor microenvironment B16F10 mouse melanoma model IL-27 induced production of antiangiogenic chemokines CXCL9 and CXCL10 by endothelial cells [31 ] Primary endothelial cells IL-27 induced CXCL9 and CXCL10 gene expression [32 ] C26 colon carcinoma cells transduced with the single-chain IL-27 cDNA IL-27-dependent tumor-specific activity and protective immunity are mediated mainly through CD8+ CTLs and production of IFN-γ [33 ] Mouse TBJ neuroblastoma cells engineered to overexpress IL-27 TBJ-IL-27 tumors showed enhanced IFN-γ and MHC class-I expression in conjunction with tumor-specific CD8+ CTL reactivity. IL-27 and IL-2 cooperated in inducing regression of metastases [34 , 35 ] Head and neck squamous cell carcinoma and IL-27 gene transfer in syngeneic mice IL-27 induced T-bet and perforin in NK cells. It inhibited the growth of NK-resistant tumors through induction of NK-mediated ADCC [36 ] Eca109 human oesophageal carcinoma cells expressing IL-27 in nude mice Tumor growth was retarded in vivo, possibly through enhanced NK cell activity and IFN-γ production [37 ] Human promonocytic cell line U937 IL-27 inhibited the M2 macrophage polarization [38 ] IL27RA(−/−) mice bred with mutant p53 heterozygous (p53(R172H/+)) mice More rapid spontaneous tumor development and reduced survival of IL27RA(−/−)p53(H/+ or H/H) mice relative to their WSX1(+/+) counterparts [39 ] J558 plasmacytoma or B16 melanoma injected in EBI3-deficient BALB/c or C57BL/6 mice, respectively Reduced antitumor immune responses and enhanced tumor growth relative to wild-type control mice. Tumors from EBI3-deficient mice contained significantly decreased proportions of CD8+ T cells and increased proportions of CD4+ FoxP3+ Treg cells [40 ]
